Interactions between steroid hormones and viral oncogenes in the pathogenesis of cervical cancer.
Steroid hormones are frequently prescribed as anticontraceptive drugs to young women. Persistent papillomavirus infections particularly with high risk virus types are very common in younger women and were shown to be the strongest risk factor for the later development of cervical cancer. Steroid hormones interfere with persistent papillomavirus infections on various levels. They enhance the expression level of two viral genes, E6 and E7, which are required for the oncogenic activities of high risk papillomaviruses. In addition, they interfere with cellular gene functions involved in cell cycle regulation and programmed cell death, for example through inhibition of p53-mediated transcriptional transactivation of genes involved in cell cycle arrest and apoptosis. Furthermore, steroids inhibit the immunologically mediated resolution of minor HPV-induced cervical lesions, particularly through inhibition of major histocompatibility class I and class II antigen expression. These observations point to potent cocarcinogenic effects of steroid hormones in persistently papillomavirus infected individuals by enhancing the transforming activities of viral oncogenes and interfering with the efficient resolution of virus infected lesions. The clinical significance of these experimental observations requires careful analysis in prospective trials.
von Knebel Doeberitz
M
M
Department of Surgery, University of Heidelberg.
Spitkovsky
D
D
Ridder
R
R
D017209:Apoptosis; D002453:Cell Cycle; D002869:Chromosome Aberrations; D003276:Contraceptives, Oral / Q000009:adverse effects; D004967:Estrogens / Q000009:adverse effects / Q000502:physiology*; D005260:Female; D016679:Genome, Viral; D006801:Humans; D009856:Oncogene Proteins, Viral / Q000235:genetics; D009857:Oncogenes; D027383:Papillomaviridae / Q000235:genetics / Q000302:isolation & purification*; D011374:Progesterone / Q000009:adverse effects / Q000502:physiology*; D012307:Risk Factors; D002578:Uterine Cervical Dysplasia / Q000209:etiology / Q000235:genetics* / Q000473:pathology / Q000821:virology; D002583:Uterine Cervical Neoplasms / Q000209:etiology / Q000235:genetics* / Q000473:pathology / Q000821:virology
D003276:Contraceptives, Oral; D004967:Estrogens; D009856:Oncogene Proteins, Viral; D011374:Progesterone